Using anti-Nk 1.1 serum, the alloantiserum specific for murine natural killer (NK) cells, we followed the ontogenetic development of NK-1+ cells in fetal thymus, liver, and spleen. A transient population of NK-1+ cells in fetal thymus was observed on day 14 but not on day 16 of gesta-tion. On day 16 of gestation NK-1+ cells were detected only in liver and spleen. The proportion of NK-1+ cells in spleen remained high (20 to 30%) at birth and persisted until 2 to 3 weeks of age. The NK-1+ cells in "baby" (1-to-2-week-old) spleen bound to YAC cells but failed to lyse them in 51Cr release assays. Upon induction with interferon (IF), the proportion of NK-1+ cells increased but the lytic activity remained low, suggesting that the "baby" NK-1+ cells are immature in lytic function. In adult mice (12-to-14-months-old), NK-1+ cells were also detectable, but NK activities were lower compared to the young adult (6-to-8-weeks-old) mice. The NK-1+ cells of old mice were readily induced by IF to exhibit NK activity and the induced NK cells were NK-1+. We have thus defined NK-1.1 antigen as an early hemopoietic differentiation antigen. Splenic NK-1- cells could be induced by IF to become NK-1+ cells, which could be either inactive or active in NK assays, dependent on the age of the mice. (LB)